Crystallographic studies are proposed to investigate the structural basis of catalysis and substrate specificity in three large enzyme-RNA complexes, for which crystals are available. Two of these projects are de novo structure determinations: E. coli cysteinyl-tRNA synthetase (CysRS) and E. coli tRNA pseudouridine synthase II (PSUII). CysRS is one of the canonical twenty aminoacyl-tRNA synthetases, which ensure fidelity of the genetic code. Complete native data to 2.7 E are presented as preliminary information. PSUII converts uridine-55 in the T-stem of tRNA to pseudouridine by a complex stereochemical pathway, which is not understood. Preliminary crystals of PSUII complexed to a 17-mer RNA corresponding to the tRNA T-arm have been obtained which diffract in-house to at least 4.5 E resolution.